title: Portal hypertension: serotonin and pathogenesis.
abstract: It has been demonstrated that serotonin (5-hydroxytryptamine; 5HT) can decrease portal vascular resistance in animals and could be a possible mediator for intestinal vasodilatation. Moreover, isolated mesenteric vein from portal hypertensive rats has been shown to be hyper-responsive to 5HT. Hence 5HT may play a role in the pathophysiology of the hyperkinetic syndrome observed in patients with portal hypertension. This hypothesis that serotonin might increase splanchnic blood flow, and hence portal pressure, led us to propose that 5HT receptor antagonists might decrease portal hypertension. We observed that acute administration of ketanserin, an antagonist of serotonin at 5HT2 receptors, significantly decreased portal pressure and portal-systemic collateral blood flow in patients with cirrhosis, whereas hepatic blood flow was not modified. Arterial pressure slightly decreased, while cardiac output was not affected by ketanserin. These findings were also observed during continuous administration of ketanserin. More recently, it has been shown that ritanserin, a more specific 5HT2 receptor antagonist, significantly decreased portal pressure in cirrhotic patients. Finally, in rats with portal hypertension, ketanserin as well as ritanserin produced significant reductions in portal pressure but did not modify portal tributory blood flow. In these portal hypertensive animals, 5HT2 antagonists may act on hepatocollateral vascular resistance. These studies confirm current evidence in favor of a role for the actions of serotonin via 5HT2 receptors in portal hypertension and add a new group of substances for its treatment.
authors.affiliation: Unité de Recherches de Physiopathologie Hépatique (INSERM U-24) Hôpital Beaujon, Clichy, France.
authors.forename: D
authors.initials: D
authors.lastname: Lebrec
mesh_terms: D000818:Animals; D006801:Humans; D006975:Hypertension, Portal / Q000503:physiopathology*; D012701:Serotonin / Q000502:physiology*
chemical_list: D012701:Serotonin